Lyme disease is a potentially severe and complex multisystem disorder associated with the tick-borne Borrelia burgdorferi toxins. The disease is transmitted to humans and other animals through arthropod bites. The Borrelia species are maintained in nature by cycling through the wild animals (e.g., deer, rodents and fowl) and the ticks that feed upon them. Lyme disease was first officially recognized in North America in 1975, and has become recognized as the most prevalent tick-borne disease in the U.S. This recognition was due to an outbreak of disease in children in Lyme, Conn. The disease is now recognized as having a worldwide distribution.
In the northeastern United States, Wisconsin and Minnesota, the deer tick, Ixodes dammini is the primary vector, while in the western United States and Europe, I. pacifious and I. ricinus are the main vectors, respectively.
The clinical symptoms of Lyme disease vary among individuals and during the time course of infection, and range from a relatively benign skin rash to severe arthritic, neurologic and cardiac manifestations. The most common clinical manifestation is the distinctive skin rash (“erythema migrans,” “erythema chronicam migrans,” or “ECM”) which follows the bite of an infected tick. This rash is often accompanied by headache, stiff neck, myalgias, arthralgias, malaise, fatigue, and/or lymph node swelling. Weeks to months later, some infected patients develop meningoencephalitis, myocarditis, or migrating musculoskeletal pain. Even later in the course of disease, patients may experience intermittent attacks of oligoarticular arthritis or chronic arthritis in large joints, particularly in the knee. Other clinical syndromes are reported that may have the same etiologic agent include lymphocytoma (lymphadenosis benigna cutis), acro-dermalitis chronica atrophicans, tick-borne meningoradiculitis (Garin-Bujadoux-Bannwarth's syndrome), and myositis. Due to increased awareness and reporting, reported cases of Lyme disease have increased over time. Between 1982 and 1992, approximately 50,000 cases of Lyme disease were reported to the Centers for Disease Control (CDC), with 48 states reporting cases by 1992.
When the risk of Lyme disease is great, oral antibiotics are frequently administered to people who have been bitten by ticks. However, liberal oral administration of antibiotics is controversial and the risk of infection has to be balanced against indiscriminate long-term treatment with antibiotics. As an alternative, the topical application of certain antibiotics (Chien-Ming Shih and Andrew Spielman, “Topical Prophylaxis for Lyme Disease after Tick Bite in a Rodent Model”, The Journal of Infectious Diseases, 1993, 168, p. 1042-1045) was evaluated and it could be shown that in a rodent model local infection was not detectable after such treatment. These studies further demonstrated, that by means of Xenodiagnosis, no B. burgdorferi were detected 28 days after the tick feeding. These findings, however, make no conclusive statement whether the transfer of B. burgdorferi from the site of infection to Borrelia's target organs can be effectively be prevented.
B. burgdorferi is presenting several morphological forms with different sensitivity to antibiotics and environmental stress, such as exposure to distilled water or freeze-thaw cycles. Cystic forms (also called spheroplasts or starvation forms) have the ability to reconvert into normal motile spirochetes both in vitro and in vivo [Brorson O. et al., Infection. 1997 July-August; 25(4):240-6]. The presence of various atypical spirochete forms: spheroplastic L (without cell walls), cystic, and granular “blebs” has also been reported. One may therefore distinguish spirochetal forms, which are linked with high metabolic and proliferative activity, from cystic and spherical forms, which are dormant with minimal biochemical activity.
In view of debilitating nature of the advanced stages of the disease, compositions and methods for disease prevention remain critical. However, these needs have not previously been satisfactorily met.